NM_006227.4:c.1322G>C

Variant names:

• chr20-45899499-C-G
• NM_006227.4:c.1322G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006227.4(PLTP):​c.1322G>C​(p.Gly441Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLTP NM_006227.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44

Genes affected

PLTP (HGNC:9093): (phospholipid transfer protein) The protein encoded by this gene is one of at least two lipid transfer proteins found in human plasma. The encoded protein transfers phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL). In addition to regulating the size of HDL particles, this protein may be involved in cholesterol metabolism. At least two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLTP	NM_006227.4	c.1322G>C	p.Gly441Ala	missense_variant	Exon 15 of 16	ENST00000372431.8	NP_006218.1
PLTP	NM_182676.3	c.1166G>C	p.Gly389Ala	missense_variant	Exon 14 of 15		NP_872617.1
PLTP	NM_001242921.1	c.1058G>C	p.Gly353Ala	missense_variant	Exon 13 of 14		NP_001229850.1
PLTP	NM_001242920.2	c.1037G>C	p.Gly346Ala	missense_variant	Exon 13 of 14		NP_001229849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLTP	ENST00000372431.8	c.1322G>C	p.Gly441Ala	missense_variant	Exon 15 of 16	1	NM_006227.4	ENSP00000361508.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1322G>C (p.G441A) alteration is located in exon 15 (coding exon 14) of the PLTP gene. This alteration results from a G to C substitution at nucleotide position 1322, causing the glycine (G) at amino acid position 441 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;.;T;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.79	D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	.;.;M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.019	D;T;D;D;T
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.99	D;.;D;D;.
Vest4		0.87
MVP		0.34
MPC		0.76
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.58
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44528138;